Acetylcholine stimulation of secretion by the exocrine cells of the pancreas is associated with enhanced turnover of phosphatidylinositol and a significant increase in the intracellular level of free inositol. High uptake of inositol by pancreatic exocrine cells has been shown to (a) alter the rate of the intracellular transport of secretory proteins in these cells and (b) stimulate secretion. The principal objectives of the proposed research are twofold: First, we want to determine in pancreatic exocrine cells where, along the secretory pathway, do high intracellular levels of free inositol either affect the rate at which secretory proteins are translocated between intracellular membrane systems or alter the nonstimulated intracellular course of the secretory proteins. Secondly, we want to determine (a) if glucose stimulation of pancreatic beta cells is associated with stimulated phosphatidylinositol turnover and a significant increase in the intracellular level of free inositol and (b) if high uptake of inositol by these cells stimulates insulin release. We thus plan to compare the roles of stimulated phosphatidylinositol turnover and increased intracellular inositol levels on the secretory process of these two cell populations of the pancreas.